C. elegans responds to the chemical repellant 1-octanol by rapidly reversing direction during locomotion. We have previously shown that response to diluted octanol is modulated by the presence or absence of food, and that the neurotransmitter serotonin is important for this modulation. We find that the neurotransmitter dopamine plays a role in modulating response to undiluted octanol when tested in the presence of food.
cat-2 animals, which are defective in dopamine biosynthesis, respond to octanol with a slight but reproducible latency compared to N2 control animals. This subtle behavioral defect is completely rescued by addition of exogenous dopamine. This result suggests that dopamine positively regulates neural signaling in the octanol-sensing chemosensory circuit. We find this somewhat difficult to reconcile with a recently published finding wherein dopamine attenuates chemosensory signaling (Ferkey et al. Neuron (2007) 53:39-52). As behavioral assays often depend on difficult to control ambient conditions, we speculate that there are as-yet unidentified environmental factors that contribute to the observed differences. In an effort to identify genes in the dopamine signaling pathway that regulates octanol response, we carried out an EMS mutagenesis screen in a
cat-2 background for mutants that fail to respond to octanol. In a preliminary screen, 4 mutants were isolated that responded significantly worse than
cat-2 control animals. Interestingly, octanol response in two of the mutants was completely restored by exogenous dopamine, whereas the other two mutants were completely resistant to exogenous dopamine. This suggests that there are other pathways parallel to dopamine signal transduction that can modulate octanol response. We are currently working on characterizing and mapping these mutant strains.